The Epidermal Growth Factor Receptor (EGFR) gene is frequently upregulated in carcinomas of the breast, kidney, ovary, cervix, and in squamous cells. The upregulation is typically due to gene amplification or overexpression. EGFR upregulation in gliomas is most often associated with the rearrangement of the EGFR gene resulting in alterations of its transcript so that such gliomas express both wild-type endogenous EGFR as well as the episomal mutant form. The most common of the rearrangements are genomic alterations leading to deletion of exons 2-7 in the EGFR mRNA (called ds 2-7 EGFR, deltaEGFR, EGFR-de2-7, or EGFRvIII), which causes an in-frame truncation of 801 bp in the extracellular domain of the molecule. The EGFR gene is amplified in >50% of glioblastomas. This amplification is often associated with expression of deltaEGFR, which conveys enhanced tumor aggressiveness.
Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism known as RNA interference (RNAi). WO 99/32619 (Fire et al.) disclosed the use of a dsRNA of at least 25 nucleotides in length to inhibit the expression of genes in C. elegans. dsRNA has also been shown to degrade target RNA in other organisms, including plants (see, e.g., WO 99/53050, Waterhouse et al.; and WO 99/61631, Heifetz et al.), Drosophila (see, e.g., Yang, D., et al., Curr. Biol. (2000) 10:1191-1200), and mammals (see WO 00/44895, Limmer; and DE 101 00 586.5, Kreutzer et al.).